In a biopharmaceutical fluid preparation process by a laboratory which prepares pharmaceutical products, it is known to receive a large amount of biopharmaceutical fluid in a sterile container appropriate for this purpose, typically holding about 10 to 20 liters, and then at the desired time to empty the container of the biopharmaceutical fluid and transfer it for further processing, typically filtration or the like, followed by final formulation or the filling of smaller capacity containers. All these operations must be performed fairly quickly for industrial reasons, and in a sterile manner. In addition, if filtration or a similar step is planned, the biopharmaceutical fluid must be under sufficient pressure beforehand to accommodate the loss of pressure at the filter.
The specific field of the invention is the preparation of a biopharmaceutical fluid by a laboratory which prepares pharmaceutical products, where the reception and then the draining and transfer concern a large amount of biopharmaceutical fluid, at least about 10 liters, for the purposes of further treatment such as filtration, final formulation, and/or filling containers of smaller capacity.
For the operations presented above, it is known to make use of a system for the reception and transfer of a biopharmaceutical fluid under controlled pressure, comprising a device for receiving then draining a biopharmaceutical fluid under controlled pressure, a means intended and suitable for supplying a pressurized compression gas having a line for injection of the pressurized compression gas, and a means for monitoring and controlling the pressure of the pressurized compression gas in the injection line. The amounts of biopharmaceutical fluid received then transferred can typically be about a liter or several tens of liters.
In a first known embodiment, the device comprises a rigid receptacle made of stainless steel, provided with a removable cover, forming an inner container intended and suitable for receiving the biopharmaceutical fluid, an inlet for filling the container with the biopharmaceutical fluid, located at the top, an outlet for draining the biopharmaceutical fluid from the container, located at the bottom, and an inlet for the pressurized draining gas. Such a device can be used repeatedly after rigorous cleaning. Such a device has the disadvantages, however, of the cleaning prior to reuse being long and expensive and meticulous, and the draining gas being in contact with the biopharmaceutical fluid which is undesirable in a sterile process.
In a second known embodiment, illustrated by U.S. Pat. No. 5,799,830, the device firstly comprises an inner bag made of flexible and fluidtight plastic, having an inner container intended and suitable for receiving the biopharmaceutical fluid, provided with a port for filling with the biopharmaceutical fluid and a port for draining the biopharmaceutical fluid, and associated with these ports, a filling tube having an inlet for filling the container with biopharmaceutical fluid and drain tube having an outlet for draining biopharmaceutical fluid from the container. The device secondly comprises a rigid external stainless steel container into which the inner container is placed, forming a compression chamber between the external container and the inner container, and the filling tube and drain tube connect, by their inlet and outlet respectively, to the outside of the external container. The external container is provided with a pressurized draining gas injection inlet in the compression chamber. With such a device, the external container can be used repeatedly, as with the first described embodiment, with the inherent disadvantages. Such a device is complex, however, since the external container must include a door for the introduction and removal of the inner bag which it must be possible to open and close in a fluidtight manner, and delivery and draining systems associated in fluid communication with the inner bag and associated in a fixed and fluidtight manner with the external container. This door and these delivery and drainage systems make it even more complex to clean the external container. Finally, the drain tube passes through the inner bag from one side to the other so that when the bag is compressed as much as possible, a residual volume remains within which is difficult or impossible to empty.
In the specific field of the invention, a need therefore exists for the ability to receive and then drain and transfer, under sufficient and controlled pressure, a large amount of biopharmaceutical fluid of at least about 10 liters.
Known from the prior art are devices and methods for the infusion of a liquid into the human body, which typically concern small amounts of liquid, less than 3 liters. Infusion devices relying on simple gravity are well known. There are also devices in which the flow rate is controlled by applying a compaction pressure to the bag containing the liquid to be infused, by means of a chamber filled with a gas as is described for example in U.S. Pat. No. 3,838,794, FR-A-2,682,602, GB 2,850,582, U.S. Pat. Nos. 5,163,909, 5,399,166, and EP 1,923,082.
Such devices and methods are not part of the specific field of the invention. With these devices and methods, unlike the field of the invention, the fluid involved is an infusion liquid or a parenteral liquid or similar, only used for delivery to a patient, typically in a healthcare center. Moreover, unlike the field of the invention, the reception and draining involve small amounts, at most 3 liters and usually much less. Finally, compared to the field of the invention, the applied pressures are much lower, and the requirements concerning delivery of the contents after draining are different.
Thus, considering only document U.S. Pat. No. 3,838,794, that document emphasized clogging of the device due to contact of the walls, a problem that may indeed arise with devices of small capacities and high flexibility but not occurring in the field of the invention where the capacities are much larger and the devices much less flexible.